This grant is based on two hypotheses derived from our preliminary results: 1) that DMAB and its analog anabaseine act through one or more brain nicotinic receptor subtypes to exert behavioral, electrophysiological, cellular and biochemical actions that may have therapeutic benefits for Alzheimer's disease and related neuropathologies; and 2) that nicotinic receptors may exert a cytoprotective action in selected neurons in the neocortex or other regions by modulating intracellular calcium levels. The first hypothesis will be tested with several standard pharmacological approaches, e.g., dose response-correlations and receptor-antagonist studies involving electrophysiology, behavior, and neurochemistry, in normal and cholinergically hypofunctional animals. The second line of studies will also use a multidisciplinary approach involving electrophysiological recording of neuronal channels sensitive to intracellular calcium concentrations and primary neocortical neuronal cultures sensitive to a cytoprotective action of nicotine.